Cell Reports (Nov 2017)

Niche Cadherins Control the Quiescence-to-Activation Transition in Muscle Stem Cells

  • Aviva J. Goel,
  • Marysia-Kolbe Rieder,
  • Hans-Henning Arnold,
  • Glenn L. Radice,
  • Robert S. Krauss

DOI
https://doi.org/10.1016/j.celrep.2017.10.102
Journal volume & issue
Vol. 21, no. 8
pp. 2236 – 2250

Abstract

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Many adult stem cells display prolonged quiescence, promoted by cues from their niche. Upon tissue damage, a coordinated transition to the activated state is required because non-physiological breaks in quiescence often lead to stem cell depletion and impaired regeneration. Here, we identify cadherin-mediated adhesion and signaling between muscle stem cells (satellite cells [SCs]) and their myofiber niche as a mechanism that orchestrates the quiescence-to-activation transition. Conditional removal of N-cadherin and M-cadherin in mice leads to a break in SC quiescence, with long-term expansion of a regeneration-proficient SC pool. These SCs have an incomplete disruption of the myofiber-SC adhesive junction and maintain niche residence and cell polarity, yet show properties of SCs in a state of transition from quiescence toward full activation. Among these is nuclear localization of β-catenin, which is necessary for this phenotype. Injury-induced perturbation of niche adhesive junctions is therefore a likely first step in the quiescence-to-activation transition.

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